CN107779399A - A kind of micro-fluidic chip imaging system for being used to monitor cellular pharmacokinetics - Google Patents

A kind of micro-fluidic chip imaging system for being used to monitor cellular pharmacokinetics Download PDF

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Publication number
CN107779399A
CN107779399A CN201610750283.0A CN201610750283A CN107779399A CN 107779399 A CN107779399 A CN 107779399A CN 201610750283 A CN201610750283 A CN 201610750283A CN 107779399 A CN107779399 A CN 107779399A
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microfluidic device
layer
detection
micro
charged particles
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CN201610750283.0A
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Chinese (zh)
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沙薇
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Henan Tiansheng Taifeng Medical Technology Co Ltd
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Henan Tiansheng Taifeng Medical Technology Co Ltd
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Priority to CN201610750283.0A priority Critical patent/CN107779399A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
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  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Toxicology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Food Science & Technology (AREA)
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  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The present invention relates to a kind of microfluid imaging system, specifically a kind of high-precision sensitive detector and micro-fluidic chip layer, applied to drug screening and accurate medical field.It passes through the functional module such as integrated multifunction micro-valve, positive electron detection, image reconstruction analysis on the basis of existing micro-fluidic chip, and unattended duty Automated condtrol is carried out using computer, develop a set of digitlization valve control biological medicine exploitation miniflow platform for integrating sample precision sample introduction, chemical reactive synthesis, bio-pharmaceutical screening, cell culture and online effect of drugs and analyzing that can be used for modern biotechnology medicine developmental research.Realize the functions such as inexpensive, high-throughout biological medicine exploitation, synthesis and screening, viral resistance screening, individuation tracking administration.

Description

A kind of micro-fluidic chip imaging system for being used to monitor cellular pharmacokinetics
Technical field
The present invention relates to a kind of microfluid imaging system, specifically a kind of high-precision sensitive detector and micro-fluidic chip Layer, applied to drug screening and accurate medical field.
Background technology
Presently the most conventional molecular imaging technology has medicine imaging technique, especially with Positron emission tomography PET's Molecular imaging research is with strongest influence power, and current Positron emission tomography technology is only limitted to human body or small animal imaging and had set The shortcomings of standby volume is big, cost is high, manipulation difficulty is big, the external cell imaging for being imaged the i.e. histotomy of excision there is no should With.Present invention incorporates micro-fluidic chip and Positron emission tomography principle, constructs collection cell culture, detection, an imaging In the external imaging system of one.
The content of the invention
By on the basis of existing micro-fluidic chip, integrated multifunction micro-valve, positive electron detect this project, image reconstruction divides The functional modules such as analysis, and unattended duty Automated condtrol is carried out using computer, develop a set of modern biotechnology that can be used for and cure Collection sample precision sample introduction, chemical reactive synthesis, bio-pharmaceutical screening, cell culture and the online effect of drugs point of medicine developmental research The digitlization valve control biological medicine analysed in one develops miniflow platform.Realize inexpensive, high-throughout biological medicine exploitation, synthesis The functions such as administration are tracked with screening, viral resistance screening, individuation.
Embodiment
As Fig. 1 right figures illustrate measurement cell pairFluorodeoxyglucose[18F] FDG absorption process:(1) loading cells To culture lattice in (2) will [18F] FDG solution introducing (3) cellular uptake [18F] FDG (4) by it is extracellular [18F] FDG solution Clean, detector only measure it is intracellular [18F] FDG concentration, and by the detection weight from the positive electron projected into the cell Build out cell image.
Explanation:[18F] FDG refers toFluorodeoxyglucose.Glucose is one of three big energy substance of human body, can be by PET is detected and is formed the positron radionuclide of image18F is marked on glucose, that is, form [18F]FDG;Because [18F]FDG It is horizontal that the glucose metabolism of intracorporeal organ/tissue can be accurately reflected, therefore be the main developer that current PET-CT is imaged;It is pernicious Tumour cell is vigorous due to being metabolized, and causes the increase in demand to glucose, most of tumor focus can show as to [18F] FDG Height intake, therefore can apply [18F] FDG imagings can accurate judgement benign tumors, pernicious and medication effect, so as to correctly referring to Lead clinical treatment decision-making.
Such as Fig. 2 Fig. 3,16 ventricular cell culture lattice are included in micro flow chip.Pass through computer control pressure level and microchannel valve Door switch, independently addressable each culture lattice;9 entrances (reagent inlets) and outlet (Outlet) port, for cell Or biological and chemical fluid inflow and outflow;Color code:Blueness represents fluid network, and red is cell culture chamber, yellow for every From valve.
Such as Fig. 4 (a) fibronectin coatings:Fibronectin solution (1 milligram of ML-1) is injected into culture lattice, with Biocompatibility (b) cell culture medium for improving environment loads (c) loading cells:Cell suspending liquid loads culture lattice by gravity It is interior, and it is maintained at the circulation and cell nursing of 37 DEG C of (d) culture mediums
As Fig. 5 cells to [18F] FDG absorption and imaging:(a) [18F] FDG incubation times be 10,30,60 and 120 Minute when, cell to [18F] FDG intakes image (b) image quantization (not yet correct nucleic decay);In each cell Radioactivity not with [18F] the certain proportionate relationship of FDG incubation times holding;The signal of rapid growth was 10 minutes and 30 minutes Peak;Due to [18F] FDG decays over time, signal continuous decrease.
For the description of test in Figure 4 and 5:
[18F] FDG intake experiment the previous day, U87 glioblastoma cells (cancer of the brain) be loaded onto 4x3 culture lattice array Micro flow chip on, so as to adaptation of the cell to microenvironment so that cell is adherent well, and loading cells flow is shown in Fig. 4;Each Culture lattice there are about 100 cells, be controlled by computer, the supply of system update DMEM culture mediums, micro flow chip when every 6 small 90. It is stored in an incubator.In experimental day, concentration be 1mCi/ml [18F] FDG solution be introduced into it is each on chip Cultivate lattice;Each file [18F] FDG is different to time of cell culture, and respectively 10,30,60,120 minutes from left to right.Often The image of individual cell culture lattice due to number of cells and [18F] FDG is to different and different (Fig. 5 (a)) of the time of cell culture; The signal quantization result that more image obtains show with Fig. 5 (b), wherein the longitudinal axis be in cell [18F] FDG concentration, transverse axis is [18F] FDG is to time of cell culture.

Claims (10)

1. this microfluidic device is characterised by, including:Cell culture layer, circuit layer and the detection of charged particles of microfluid Layer.Detection of charged particles layer is positioned close to the circuit layer of described microfluid.In operation, detection of charged particles Layer Detection is micro- One two dimensional image of charged particle and formation that electromagnetic radiation in the circuit layer of fluid goes out.
2. the microfluidic device as described in 1, it is characterised in that the charged particle detector layer includes scintillator crystal materials.
3. the microfluidic device as described in 2, it is characterised in that:Described scintillator material is cesium iodide crystal.
4. the microfluidic device as described in 2, it is characterised in that the scintillation material is that a kind of crystal with micro- column structure is used To guide the direction of light.
5. the microfluidic device as described in 2, it is characterised in that also include the detecting system to be communicated with the scintillation material, it is described Detecting system is used to detect light caused by scintillation material, and light excites generation by charged particle caused by scintillation material.
6. the microfluidic device as described in 5, it is characterised in that detecting system includes an imaging sensor and lens combination, thoroughly Mirror system is placed between scintillation material and imaging sensor to be imaged the light beam projected from scintillator to imaging sensor.
7. the microfluidic device as described in 5, it is characterised in that the detecting system includes a fibre optic plate, and fibre optic plate is arranged on institute State on detection of charged particles layer, imaging sensor is arranged on fibre optic plate.
8. the microfluidic device as described in 1, it is characterised in that the detection of charged particles layer includes a semiconductor detector.
9. the microfluidic device as described in 1, it is characterised in that the detection of charged particles layer includes the snowslide of a position sensing Photodiode.
10. the microfluidic device as described in 9, in addition to a light shielding layer are placed in above the detection of charged particles layer, described Light shield layer is shielding the light sent from the avalanche photodide of the position sensing.
CN201610750283.0A 2016-08-30 2016-08-30 A kind of micro-fluidic chip imaging system for being used to monitor cellular pharmacokinetics Pending CN107779399A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109254018A (en) * 2018-09-11 2019-01-22 华中科技大学同济医学院附属协和医院 A kind of pharmacokinetics image-forming detecting system of radiopharmaceutical
CN114438161A (en) * 2022-01-30 2022-05-06 华中科技大学同济医学院附属协和医院 Method and system for monitoring influence of drugs on biological sample and radioactive probe

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109254018A (en) * 2018-09-11 2019-01-22 华中科技大学同济医学院附属协和医院 A kind of pharmacokinetics image-forming detecting system of radiopharmaceutical
CN114438161A (en) * 2022-01-30 2022-05-06 华中科技大学同济医学院附属协和医院 Method and system for monitoring influence of drugs on biological sample and radioactive probe
CN114438161B (en) * 2022-01-30 2024-05-03 华中科技大学同济医学院附属协和医院 Method and system for monitoring drug effect on biological sample and radioactive probe action

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